Teratogenicity will be discussed at the committee review. The briefing materials note that preliminary results from three studies conducted since the previous advisory committee meeting "were consistent in demonstrating a lack of association between topiramate exposure and risk of major congenital malformations."
However, the agency points out that "depending on the analysis, topiramate monotherapy exposure in pregnancy is likely to be associated with a two- to fivefold increased prevalence of oral clefts."
The FDA is asking the committee to consider the risk of oral clefts in babies born to women taking topiramate and a proposed Qnexa risk evaluation and mitigation strategy (REMS).
The agency has proposed and the company has agreed to a REMS that includes certification of pharmacies that dispense the drug and voluntary training of health care providers to support their risk/benefit discussions with women of childbearing potential.
Certified pharmacies would be required to remind women of childbearing potential to use contraception and to test for pregnancy. The drug could be shipped directly to the patients or to a nearby pharmacy for pickup.
The FDA’s division of risk management suggested that restricted distribution of Qnexa with mandatory pregnancy testing would have limited impact because the same restrictions are not required when topiramate is used for seizures or migraine prophylaxis. Doctors also could bypass the REMS by prescribing the topiramate and phentermine individually, the division noted.
The impact on other topiramate prescriptions was a factor for the agency. To impose the same restrictions on topiramate used for epilepsy and migraine would impose an undue burden for patients with those conditions, the division said.
Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.